Biomarkers are a measurable indicator that may be used to precisely, reproducibly, and objectively reveal any molecular species found to provide correlation to a particular phenotype or perturbation of a biological system. For example, biomarkers may be used to distinguish a normal biological state from a pathological state. Biomarkers may also be used to detect a response to a specific therapeutic intervention (Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther. 69, 89-95 (2001)); to predict survival (prognostic biomarkers); to assess drug safety and evaluate target engagement and immediate consequence on biological processes (pharmacodynamics biomarkers); to identify patients who are more likely to benefit from a treatment (predictive or companion biomarkers when associated with a specific therapeutic agent); to predict outcome given the response to therapy (surrogate biomarkers); and to monitor disease progression or therapeutic efficacy (monitoring biomarkers) (Pragmatic issues in biomarker evaluation for targeted therapies in cancer. Armand de Gramont, Sarah Watson, Lee M. Ellis, Jordi Rodin, Josep Tabernero, Aimery de Gramont & Stanley R. Hamilton Nature Reviews Clinical Oncology 12, 197-212 (2015) doi: 1 0.1038/nrclinonc.2014.202). For example, biomarkers may be used to detect individuals who have a disease (e.g. cancer), infection (e.g. bacterial DNA, viral DNA, or antibody response), systemic breakdown (e.g. sepsis), environmental exposure (e.g. lead), are at risk for developing a disease (e.g. tuberculosis) or have experienced traumatic physiological event (e.g. heart attack).
Timely detection and quantification of disease biomarkers can be used to detect diseases at early stages of development, when they are frequently the most treatable or preventable. They are also increasingly necessary in personalized medicine, identifying the population of patients most likely to benefit from targeted therapies. Early identification of disease and target populations' most likely to benefit from treatment decreases mortality, cost, and in the case of infection, decreases the development of multi-drug resistant organisms. Point of care devices based on detection of biomarkers permit robust, low-cost and real-time rapid identification of a diseased state under a variety of conditions, allowing for enhanced monitoring and timely therapeutic changes.
In addition to biomarkers, there is a need for means for the rapid detection in small samples of other target analytes such as proteins, pathogens, heavy metal ions, small molecules, DNA, RNA, SNPs, microbes, agrochemicals, and hydrocarbons in environmental samples such as water, soil, food, beverages, building products, bulk chemicals or reagents. Current testing methods for biomarkers and analytes require large samples of the compound being tested. For example, standard samples for biomarker testing are at least 2 mL. Furthermore, current testing methods have limited sensitivity, requiring a relatively large amount of the biomarkers or analytes of interest to be present in order to be detected. There is therefore a need for compositions and methods for detecting small amounts of targets of interest in small samples.